Mosquito-borne diseases continue to cause significant morbidity and mortality worldwide despite on-going control efforts. In 2015, there were >200 million cases of malaria worldwide, causing nearly half a million deaths, with most of the deaths occurring among children under the age of 5 years. Mosquitoes also transmit arboviruses, including dengue, yellow fever, West Nile virus, chikungunya, Rift Valley fever, Japanese encephalitis, and Zika virus. The recent outbreak of Zika virus in Central and South America, as well as the Caribbean, serves as a reminder of how quickly these viruses can spread and how difficult they can be to control. We completed a Phase I study of a novel universal mosquito-borne disease vaccine and are now preparing a manuscript. Through modulation of the immune system after a mosquito feeding, this vaccine targets the vector saliva and may provide prophylaxis against multiple arboviral and protozoal diseases. In addition the vaccine potentially leads to a reduced mosquito lifespan after feeding therefore also reducing transmission of these diseases. This protocol marks the first time a vaccine targeting mosquito saliva has been tested in humans and the first time clean mosquito feedings on humans have been performed in the NIH Clinical Center. As a continuation of our close collaboration with LMVR we were awarded an NIH Bench To Bedside award and in the past year have completed enrollment of a follow up clinical study in the NIH Clinical Center to evaluate the effect on the immune response of multiple exposures to the same vector. This study included the evaluation of two species of mosquito as well as sandflies, the vector of leishmania. We expect the final data from this study to be instrumental in further understanding how vaccination strategies that target vector saliva may work in individuals from endemic disease areas. We expect to complete the analysis during the next year. During the next year we will complete a third clinical trial, a follow up study to our initial study of AGS-v with an updated version of the vaccine AGS-v Plus. This Phase Ib study will be completed in collaboration with LMVR and University of Maryland under a CRADA agreement. We have initiated the study and expect to fully enroll in the next 6-8 months. This study should continue the clinical development of this unique vaccine strategy we initiated in 2018.